Waymon then applied for a scholarship to study at the prestigious Curtis Institute of Music in Philadelphia, where she was denied admission despite a well-received audition. Waymon became fully convinced this rejection had been entirely due to racial discrimination. Years later, nine days before her death, the Curtis Institute of Music bestowed on her an honorary degree.

To make a living, Eunice Waymon changed her name to "Nina Simone". The change related to her need to disguise herself from family members, having chosen to play "the devil's music" or "cocktail piano" at a nightclub in Atlantic City. She was told in the nightclub that she would have to sing to her own accompaniment, and this effectively launched her career as a jazz vocalist.

Simone recorded more than 40 albums, mostly between 1958, when she made her debut with Little Girl Blue, and 1974. She had a hit in the United States in 1958 with "I Loves You, Porgy".